Malignant Peripheral Nerve Sheath Tumor

Malignant Peripheral Nerve Sheath Tumor

David R. Lucas, MD

Cyril Fisher, MD, DSc, FRCPath

MPNSTs often arise from a major nerve trunk, such as this sciatic nerve tumor forming a fusiform, lobulated, intraneural mass image. MPNSTs can extend along the nerve to form satellite nodules image.

Microscopically, MPNSTs are highly variable in appearance and degree of differentiation. Well-differentiated tumors have spindle cells with tapered and wavy nuclei and indistinct cytoplasm, as shown.



  • Malignant peripheral nerve sheath tumor (MPNST)


  • Neurofibrosarcoma, malignant schwannoma, neurogenic sarcoma


  • Sarcoma arising from a nerve or benign nerve sheath tumor or showing nerve sheath cellular differentiation

    • Diagnostic criteria

      • Arises from a nerve or benign nerve sheath tumor

      • Or shows histological evidence of nerve sheath differentiation in a NF1 patient

      • Or shows histological plus immunohistochemical or ultrastructural evidence of nerve sheath differentiation in non-NF1 patient


Genetic Predisposition

  • 50% associated with neurofibromatosis type 1 (NF1)

    • Lifetime incidence: 2-16%

  • 40% sporadic

Environmental Exposure

  • 10% associated with radiation

Molecular Pathogenesis

  • NF1 caused by germline mutation of NF1 tumor suppressor gene

    • Somatic loss of 2nd NF1 allele required for tumorigenesis

  • Malignant transformation in both NF1-associated and sporadic MPNST often involves INK4A and P53 and their downstream pathways



  • Incidence

    • Rare: 5-10% of soft tissue sarcomas

  • Age

    • Mostly adults (20-50 years)

      • Wide age range: 10-70 years

      • Average age in NF1: 30 years

      • Average age in sporadic MPNST: 40 years

  • Gender

    • Women and men roughly equal


  • Common sites: Thigh, buttock, trunk, upper arm, retroperitoneum, head and neck

    • Mostly deep-seated

    • Central body axis more common in NF1

  • Most (70%) arise in major nerve trunks

    • Sciatic nerve most common

    • Brachial plexus, sacral plexus, paraspinal nerves


  • Painful mass

  • Neurological deficit in some


  • Surgical approaches

    • Wide excision/resection

    • Amputation

  • Adjuvant therapy

    • Radiation

  • Drugs

    • Generally poor response to chemotherapy


  • Poor

    • Local recurrence: > 40%

    • Metastasis: 30-60%

      • Lungs, bone, pleura most common

    • > 60% die of disease

    • 5-year survival: 15-34%

    • NF1 patients have worse overall prognosis

      • Probably due to higher incidence of large, central axis tumors


General Features

  • Morphology

    • Large heterogeneous mass

    • Fusiform mass within major nerve trunk


General Features

  • Similar to other soft tissue sarcomas

    • Pseudoencapsulated

    • Gray-tan

    • Firm to fleshy

    • Necrosis and hemorrhage common

  • Fusiform or eccentric mass when arising in major nerve trunk

  • Coexisting neurofibroma in some

    • Solitary or plexiform


  • Most > 5 cm

  • Sometimes very massive


Histologic Features

  • Wide spectrum of cytoarchitectural patterns

    • Mostly high-grade sarcomas

      • High mitotic rate and necrosis

      • Only around 15% are low grade

    • Nerve sheath differentiation

      • Nuclear palisading uncommon (15%), usually focal

      • Tactoid differentiation with whorling or Wagner-Meissner-like features

    • Intraneural tumors

      • Plexiform architecture

      • Microscopic extension within nerve fascicle

    • Tumors arising from preexisting benign nerve sheath tumor

      • Neurofibroma most common, transitional areas, usually in NF1 patients

      • Schwannoma, ganglioneuroma, ganglioneuroblastoma, or pheochromocytoma; very rare

    • Diffuse sarcomatous proliferation with no evidence of nerve or nerve sheath origin

  • Spindle cell MPNST (80%)

    • Long fascicles of uniform, closely spaced, hyperchromatic spindle cells

    • Alternating cellular fascicles and hypocellular areas (“tapestry” or “marbled” pattern)

    • Storiform arrays

    • Small round blue cells

    • Pleomorphic cells

      • Multinucleated giant cells

    • Extensive necrosis with perivascular preservation

    • Hemangiopericytoma-like vascular pattern in some

  • Epithelioid MPNST (5%)

    • Multinodular architecture

    • Cords and clusters in some

    • Large epithelioid cells

      • Abundant eosinophilic cytoplasm

      • Large vesicular nuclei with macronucleoli

      • Clear cytoplasm in some

    • Often mixed with spindle cells

  • Heterologous differentiation (15%)

    • Osseous and osteosarcomatous

    • Chondroid and chondrosarcomatous

    • Rhabdomyosarcomatous (Triton tumor)

    • Angiosarcomatous

    • Glandular

    • Neuroepithelial (rosettes)

Cytologic Features

  • Spindle cells

    • Ill-defined cytoplasm

    • Hyperchromatic nucleus with dispersed coarse chromatin

    • Tapered and wavy nuclei in well-differentiated tumors

    • Very brisk mitotic activity in high-grade tumors

  • Epithelioid cells

    • Abundant eosinophilic or clear cytoplasm

    • Vesicular nucleus with prominent inclusion-like nucleolus



  • S100 protein(+) in about 60%, usually focal

  • Nestin(+) in 50-80%


  • Complex structural and numeric chromosomal abnormalities

    • Frequent loss of NF1 at 17q11

    • Frequent loss of P53 at 17q13


Monophasic or Poorly Differentiated Synovial Sarcoma

  • Nuclei have softer, less coarse chromatin

  • Usually has lower mitotic rate

  • TLE1(+)

    • MPNST rarely (2%) positive

  • Usually cytokeratin(+) and EMA(+)

    • MPNST usually negative

  • Usually S100(-)

  • t(X:18) by cytogenetics

  • SYT break apart by FISH

  • SSX-SYT fusion by RT-PCR

Cellular Schwannoma

  • Usually located in retroperitoneum, pelvis, posterior mediastinum

  • Exclusively Antoni A areas; often lacks Verocay bodies

  • Necrosis and mitotic figures present

  • Can erode/destroy bone

  • Lacks malignant cytological atypia

  • Strong, diffuse S100 staining

    • MPNST usually has only focal staining

Atypical Neurofibroma

  • Large, hyperchromatic spindle cells

  • Degenerated (smudged) chromatin

  • Low miotic rate

  • Usually retains cytoarchitectural features of neurofibroma

    • Edematous fibrillary or myxoid matrix with collagen bundles (“shredded carrots” pattern)

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Jul 9, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Malignant Peripheral Nerve Sheath Tumor

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